Anders Thorell

Insulin resistance: a marker of surgical stress.

Elective surgery causes a marked, transient reduction in insulin sensitivity. The degree of the reduction is related to the magnitude of the operation. The type and duration of surgery performed, perioperative blood loss, and also the degree of postoperative insulin resistance have significant influences on the length of hospital stay. A novel approach to minimize insulin resistance after surgery is being presented and suggests that simply pretreating the elective surgical patient with sufficient amounts of carbohydrates instead of fasting can significantly reduce postoperative insulin resistance. It is not clear which mediators are the most important for the development of insulin resistance after surgery. Nevertheless, marked insulin resistance can develop after elective surgery without concomitant elevations in cortisol, catecholamines or glucagon. The main sites for insulin resistance seem to be extrahepatic tissues, probably skeletal muscle, where preliminary data suggest that the glucose transporting system is involved.

Adherence to the Enhanced Recovery After Surgery Protocol and Outcomes After Colorectal Cancer Surgery

OBJECTIVES To study the impact of different adherence levels to the enhanced recovery after surgery (ERAS) protocol and the effect of various ERAS elements on outcomes following major surgery. DESIGN Single-center prospective cohort study before and after reinforcement of an ERAS protocol. Comparisons were made both between and across periods using multivariate logistic regression. All clinical data (114 variables) were prospectively recorded. SETTING Ersta Hospital, Stockholm, Sweden. PATIENTS Nine hundred fifty-three consecutive patients with colorectal cancer: 464 patients treated in 2002 to 2004 and 489 in 2005 to 2007. MAIN OUTCOME MEASURES The association between improved adherence to the ERAS protocol and the incidence of postoperative symptoms, complications, and length of stay following major colorectal cancer surgery was analyzed. RESULTS Following an overall increase in preoperative and perioperative adherence to the ERAS protocol from 43.3% in 2002 to 2004 to 70.6% in 2005 to 2007, both postoperative complications (odds ratio, 0.73; 95% confidence interval, 0.55-0.98) and symptoms (odds ratio, 0.53; 95% confidence interval, 0.40-0.70) declined significantly. Restriction of intravenous fluid and use of a preoperative carbohydrate drink were major independent predictors. Across periods, the proportion of adverse postoperative outcomes (30-day morbidity, symptoms, and readmissions) was significantly reduced with increasing adherence to the ERAS protocol (>70%, >80%, and >90%) compared with low ERAS adherence (<50%). CONCLUSION Improved adherence to the standardized multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery, indicating a dose-response relationship.

A Carbohydrate-Rich Drink Reduces Preoperative Discomfort in Elective Surgery Patients

We studied the effects of different preoperative oral fluid protocols on preoperative discomfort, residual gastric fluid volumes, and gastric acidity. Two-hundred-fifty-two elective abdominal surgery patients (ASA physical status I–II) were randomized to preparation with a 12.5% carbohydrate drink (CHO), placebo (flavored water), or overnight fasting. The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery. Visual analog scales were used to score 11 different discomfort variables. CHO did not increase gastric fluid volumes or affect acidity, and there were no adverse events. The visual analog scale scores in a control situation were not different between groups. During the waiting period before surgery, the CHO-treated group was less hungry and less anxious than both the other groups (P ≤ 0.05). CHO reduced thirst as effectively as placebo (P < 0.0001 versus Fasted). Trend analysis showed consistently decreasing thirst, hunger, anxiety, malaise, and unfitness in the CHO group (P < 0.05). The Placebo group experienced decreasing unfitness and malaise, whereas nausea, tiredness, and inability to concentrate increased (P < 0.05). In the Fasted group, hunger, thirst, tiredness, weakness, and inability to concentrate increased (P < 0.05). In conclusion, CHO significantly reduces preoperative discomfort without adversely affecting gastric contents.

Preoperative oral carbohydrate administration reduces postoperative insulin resistance

UNLABELLED Infusions of carbohydrates before surgery reduce postoperative insulin resistance. We in-vestigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative metabolism. METHOD Insulin sensitivity, glucose turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery. The drink group (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100 g carbohydrates), as well as another 400 ml (50 g carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7) was operated after an overnight fast. RESULTS After surgery, energy expenditure increased in both groups. Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups (P < 0.05). The supressibility of endogenous glucose production by the two step insulin infusion was similar pre-and postoperatively in both groups. At the high insulin infusion rate postoperatively, whole body glucose disposal was more reduced in the fasted group (-49 +/- 6% vs -26 +/- 8%, P < 0.05 vs drink). Furthermore, during high insulin infusion rates, glucose oxidation decreased postoperatively only in the fasted group (P < 0. 05) and postoperative levels of fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor postoperative changes in cortisol and glucagon were found and no differences were found between the treatment groups. CONCLUSIONS Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast.

Preoperative Gastric Emptying Effects of Anxiety and Oral Carbohydrate Administration

BackgroundOvernight fasting is routine before elective surgery. This may not be the optimal way to prepare for surgical stress, however, because intravenous carbohydrate supplementation instead of fasting has recently been shown to reduce postoperative insulin resistance. In the current study, gastric emptying of a carbohydrate-rich drink was investigated before elective surgery and in a control situation. MethodsTwelve patients scheduled for elective surgery were randomly given 400 mL of either a carbohydrate-rich drink (285 mOsm/kg, 12.0% carbohydrates, n = 6) or water 4 hours before being anesthetized. Gastric emptying was measured (gamma camera, 99Tcm). Each patient repeated the protocol postoperatively as a control. All values were presented as the mean ± SEM by means of a nonparametric statistical evaluation. ResultsDespite the increased anxiety experienced by patients before surgery (p < 0.005), gastric emptying did not differ between the experimental and control situations. Initially, water emptied more rapidly than carbohydrate. However, after 90 minutes, the stomach was emptied regardless of the solution administered (3.2 ± 1.1% [mean ± SEM] remaining in the stomach in the carbohydrate group versus 2.3 ± 1.2% remaining in the stomach in the water group). ConclusionsPreoperative anxiety does not prolong gastric emptying. The stomach had been emptied 90 minutes after Ingestion of both the carbohydrate-rich drink and water, thereby indicating the possibility of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery.

Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy

A carbohydrate‐rich drink (CHO) has been shown to reduce preoperative discomfort. It was hypothesized that it may also reduce postoperative nausea and vomiting (PONV).

Laparoscopic Cholecystectomy Versus Mini-Laparotomy Cholecystectomy: A Prospective, Randomized, Single-Blind Study

ObjectiveTo analyze outcomes after open small-incision surgery (minilaparotomy) and laparoscopic surgery for gallstone disease in general surgical practice. MethodsThis study was a randomized, single-blind, multicenter trial comparing laparoscopic cholecystectomy (LC) to minilaparotomy cholecystectomy (MC). Both elective and acute patients were eligible for inclusion. All surgeons normally performing cholecystectomy, both trainees under supervision and consultants, operated on randomized patients. LC was a routine procedure at participating hospitals, whereas MC was introduced after a short training period. All nonrandomized cholecystectomies at participating units during the study period were also recorded to analyze the external validity of trial results. The randomization period was from March 1, 1997, to April 30, 1999. ResultsOf 1,705 cholecystectomies performed at participating units during the randomization period, 724 entered the trial and 362 patients were randomized to each of the procedures. The groups were well matched for age and sex, but there were fewer acute operations in the LC group than the MC group. In the LC group 264 and in the MC group 150 operations were performed by surgeons who had done more than 25 operations of that type. Median operating times were 100 and 85 minutes for LC and MC, respectively. Median hospital stay was 2 days in each group, but in a nonparametric test it was significantly shorter after LC. Median sick leave and time for return to normal recreational activities were shorter after LC than MC. Intraoperative complications were less frequent in the MC group, but there was no difference in the postoperative complication rate between the groups. There was one serious bile duct injury in each group, but no deaths. ConclusionsOperating time was longer and convalescence was smoother for LC compared with MC. Further analyses of LC versus MC are necessary regarding surgical training, surgical outcome, and health economy.

Exercise and insulin cause GLUT-4 translocation in human skeletal muscle.

Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU ⋅ kg-1 ⋅ min-1). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (V˙o 2 max), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia ∼56 μU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU. kg(-1). min(-1)). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (VO(2 max)), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia approximately 56 microU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.

Randomized clinical trial of the effect of preoperative oral carbohydrate treatment on postoperative whole-body protein and glucose kinetics

Preoperative oral carbohydrate (CHO) reduces postoperative insulin resistance. In this randomized trial, the effect of CHO on postoperative whole‐body protein turnover was studied.

Randomized clinical trial of the effects of immediate enteral nutrition on metabolic responses to major colorectal surgery in an enhanced recovery protocol

The effects of immediate postoperative enteral nutrition on postoperative nitrogen balance and insulin resistance were studied in patients subjected to an enhanced‐recovery protocol.